Fungal polyketides are a family of secondary metabolites all synthesized by molds from acetate. A number of them, such as aflatoxins and sterigmatocystin, have been identified as widespread mycotoxins responsible for high incidence of human diseases including cancer, large number of animal deaths, and significant loss in agricultural productivity. In this proposed research, the biosynthetic mechanisms of aflatoxins will be used as a model to elucidate biochemical events involved in the synthesis of fungal polyketides, the metabolic fate of aflatoxins and sterigmatocystin in the Rhesus monkey will be determined under conditions which simulate actual human exposures to establish their mode of action and to estimate human responses to these toxins, and the chicken embryos and the auxotrophic mutants of bacteria will be used to determine the acute toxicity, teratogenicity, mutagenicity, and carcinogenicity of the biosynthetic intermediates and the monkey metabolites of aflatoxins and sterigmatocystin. Thus, for those fungal polyketides deemed significant, research priorities can be established and areas of further investigation can be defined. The overall objective is to expedite discovery and control of toxic fungal polyketides as food borne mycotoxins.